We continue to participate in the many projects relating to the analysis of peptides and proteins that have been brought to our attention by researchers at NHLBI and NIH. The goal is still to use advanced mass spectrometric technology to study the biochemistry of a particular system by obtaining information on the identity of proteins either through mass spectrometric MS/MS sequencing or by simply carefully measuring the masses of the protein itself. This technique is unique in identifying post-translational modifications (PTMs) essential for protein/cellular functions. With the state-of-the-art Micromass QTOF3 mass spectrometer and other LC-MS and MALDI-TOF instruments, we are able to perform many experiments on biological samples, mostly in this protein and peptide class. In addition,we seek new chemical methods to enhance the search routines in order to increase their reliability. Currently, our identification of myosin heavy chain IIA as an antigen involved in chronic cytoplasmic leukemia is completed and in press. More recently we have identified the molecular weights of several intact proteins using LCMS during their preparation by Tjandra's group. These include Rec Q with its Histag and without a peptide (Keir Neuman) Sprouty (M.-P. Strub), and Glu R2, NRI (J. Lee). In addition, we are investigating the structure of a unique sequence inhibitor from E. coli (F. Portugal, U. of Maryland). Recently we have examined the HILLIC LC-MS technique as a means to characterize several glycosamino glycans (H. Katagari, H. Geller, NHLBI). [unreadable] We continue to spend a significant amount of time optimizing the sensitivity and resolution of our QTOF3,its capillary LC and its communication with the mass spectrometer, in particular with regard to its ability to analyze proteins as opposed to peptides.